The overriding objective of all hemodynamic control systems is to regulate cardiovascular performance. This may be accomplished by controlling only a limited number of motor responses, including peripheral reactions influencing the resistance and capacitance of peripheral blood vessels and reactions of the heart regulating cardiac output. Control of cardiac, rather than peripheral, motor responses is most advantageous in terms of effectiveness and feasibility. Because the objective of a hemodynamic control system is to supply the body with a sufficient quantity of oxygenated blood, cardiac output, the amount of blood flowing from the heart per unit of time, is the fundamental measurement of interest in implantable cardiac assist devices and the best indicia for determining blood supply adequacy. When an accurate measurement of cardiac output is available, a cardiac assist device can assess whether the cardiovascular system is adequately supporting the needs of the body.
There are two mechanisms for regulating the output of the heart, controlling the heart rate and modifying the stroke volume (the volume of blood ejected during each heart beat). Since cardiac output is the multiplication product of heart rate and stroke volume, regulating heart rate by means of electrical stimulation or pacing would appear to directly determine the heart's output. In fact, heart rate variations also influence stroke volume Heart rate relates to cardiac output in a more complex manner. The influence of heart rate to increase or decrease cardiac output depends on the relative amplitude of changes in rate and stroke volume. A device can alter stroke volume by modifying either mechanical or contractile influences on the behavior of the cardiovascular system. A hemodynamic control system may control both the mechanical influences (such as the degree of ventricular diastolic filling prior to ejection, and the strength of the peripheral vascular resistance) and the contractility of the cardiac muscle tissue, by regulating cardiovascular drug dosages or by modulating heart rate, normally by applying electrical stimulation.
The influences of mechanical and contractility factors on stroke volume are closely intertwined, with no single influence determining the resulting flow. For example, changes in heart rate affect mechanical influences on stroke volume because they lead to variations in the amount of ventricular diastolic filling. Likewise, control of heart rate affects cardiac contractility. Increasing and decreasing heart rate from a previously sustained level increases the strength of cardiac contraction. For transient changes in heart rate, an increasing heart rate promotes contractility for rates up to a physiological limit at which further heart rate elevations cause a reduction in contractility. The complexity of the heart rate/cardiac output relationship warrants the measurement of cardiac output and its usage as a hemodynamic control variable in a closed-loop control system.
The fundamental advantage of a hemodynamic control method based on the measurement of cardiac output and its usage to control a cardiac assist device is illustrated by the three-phase relationship between cardiac output and pacing rate shown in a report by J. L. Wessale et al., entitled "Cardiac Output Versus Pacing Rate At Rest And With Exercise In Dogs With AV Block", PACE, Vol. 11, page 575 (1988). At low pacing rates (first phase), the cardiac output increases proportional to pacing rate. At some point (second phase), further increases in pacing rate cause the cardiac output to rise only slightly, if at all. At still higher pacing rates (third phase), further increases will cause the cardiac output to diminish The width of the second phase is considered an indication of the pumping capacity of the ventricles and the health of the heart. Rate-responsive pacemakers cannot determine the phase of the cardiac output/pacing rate relationship for a given pacing rate without measuring cardiac output.
Some prior art devices measure physiological and physical parameters other than cardiac output, and regulate hemodynamics accordingly. Hemodynamic control in such devices is performed in an open-loop, rather than a closed-loop, manner since the relationship between the actual hemodynamic state, as defined by the cardiac output, and the measured control parameter is not known. The response of such devices is less directly related to the response of the heart since the hemodynamic status is characterized by a parameter related only secondarily to such status. The prior art includes a number of pacemakers, called rate-responsive pacemakers, each of which adjusts the heart rate of a patient based on a measurement acquired using a sensor to derive a parameter related in some manner to metabolic demand. Cardiac electrical activity (either stimulated or natural), body motion, respiration and temperature are examples of such parameters for assessing metabolic demand in a cardiac control device.
The method of determining metabolic demand using each of these measured parameters requires the previous correlation of the parameter with cardiac output by means of clinical experimentation. These correlation relationships are subject to wide variability from patient to patient and from one test to the next in an individual patient. More importantly, each of the parameters is subject to influences from physiological and physical sources which are unrelated to cardiac output and metabolic demand. The influences affecting these measurements are poorly understood and difficult to characterize. Furthermore, since the secondarily-related metabolic indicator pacing rates do not take the actual output from the heart into account, they may actually hinder the ability of the heart to meet the necessary metabolic demand, as illustrated in the aforementioned report by Wessale. As a consequence, all sensing and control means using a control parameter which is secondarily related to cardiac output and metabolic demand suffer from the inability to assess the hemodynamic status of the cardiovascular system.
Dual chamber heart pacers have been developed in order to generate sequential atrial and ventricular pacing pulses which closely match the physiological requirements of a patient. A conventional dual chamber heart pacer, as disclosed in U.S. Pat. No. 4,429,697 to Nappholz et al., dated Feb. 7, 1984, and entitled "Dual Chamber Heart Pacer with Improved Ventricular Rate Control," includes atrial and ventricular beat sensing and pulse generating circuits. It is known that the detection of a ventricular beat or the generation of a ventricular pacing pulse initiates the timing of an interval known as the V-A delay. If an atrial beat is not sensed prior to expiration of the V-A delay interval, then an atrial pacing pulse is generated. Following the generation of an atrial pacing pulse, or a sensed atrial beat, an interval known as the A-V delay is timed. If a ventricular beat is not sensed prior to the expiration of the A-V delay interval, then a ventricular pacing pulse is generated. With the generation of a ventricular pacing pulse, or the sensing of a ventricular beat, the V-A delay timing starts again. This patent describes how the V-A delay timing interval may be divided into three parts; the atrial refractory period, the Wenkeback timing window, and the P-wave synchrony timing window. It outlines the importance of controlling rate in order to maintain synchrony between the atrium and the ventricle. The patent does not, however, address the issue of sensing the metabolic demand of the patient and distinguishing between high atrial rates due to pathological tachycardia and high atrial rates expected when the patient exercises. The dual chamber pacer, under the influence of atrial control, may correctly set a high heart rate when it senses heightened electrical activity resulting from normal physical exertion. When the same sensing system detects a heightened electrical activity arising from a pathological tachycardia episode, having similar electrical frequency and amplitude characteristics, it will incorrectly elevate the heart rate, endangering the health of the patient.
In other examples, it is known in the prior art to electrically sense and measure natural or evoked (stimulated) cardiac potentials and analyze these signals to derive parameters such as Q-T intervals or evoked potential depolarization gradients. These are disclosed, respectively, in Rickard's U.S. Pat. No. 4,527,568, entitled "Dual Chamber Pacer with Alternative Rate Adaptive Means and Method", issued Jul. 9, 1985, and in Callaghan's U.S. Pat. No. 4,766,900, entitled "Rate Responsive Pacing System using the Integrated Cardiac Event Potential", issued Aug. 30, 1988. The efficacy of this sensing and control method depends largely on the signal amplitude and timing characteristics of the cardiac repolarization waveform, which is erratically influenced by many physiological, pharmacological and electrical phenomena. These phenomena are poorly understood, frequently leading to an unstable control behavior in devices using such sensing and control methods.
It is known in the prior art of cardiac pacemakers to control pacing rate based on the determination of cardiac output. In one example (Salo et al. in U.S. Pat. No. 4,686,987, entitled "Biomedical Method and Apparatus for Controlling the Administration of Therapy to a Patient in Response to Changes in Physiological Demand", issued Aug. 18, 1987), the device estimates cardiac output using intracardiac impedance measurements between two spaced electrodes disposed within the right ventricular cavity. This apparatus measures the tissue impedance by injecting subthreshold (non-stimulating) electrical current pulses into the body through one electrode and detecting the current at the second electrode. From changes in impedance, this device estimates changes in left ventricle volume by integrating the measurements over time, leading to the estimation of cardiac output. Unfortunately, inherent in the usage of impedance as a control parameter is the lack of a reliable relationship between impedance and actual cardiac output sought as the basis for control. When a device measures impedance using only two electrodes, gross volume approximation errors occur which are magnified during the integration process leading to the determination of cardiac output. In addition, since the electrodes are necessarily implanted into the right rather than the left ventricle (the left ventricle is not available for access) and the estimate of left ventricular volume in this manner is very crude and inaccurate, the cardiac output estimate derived using impedance techniques is highly susceptible to cumulative errors in each of the integration steps. Furthermore, extraneous influences on the impedance signal such as noise from respiration, changes in the patient's posture, and electrical interference produce a large noise signal and lead to further errors.
One recent development in cardiac monitoring and control is the implantable pressure sensor. Schroeppel describes one example of such control in U.S. Pat. No. 4,708,143, entitled "Method for Controlling Pacing of a Heart in Response to Changes in Stroke Volume", issued Nov. 24, 1987. Existing cardiac control systems using pressure sensors measure atrial and venous pressures to determine absolute and relative pressure changes during the cardiac cycle, to measure time intervals between electrophysiological phenomena, and to derive an estimate of cardiac output or stroke volume from these measurements. Pressure sensors, even when used in the most effective manner, are implantable only in locations which allow direct measurement of pressure within the right heart, rather than in the left ventricle. Measurements from the right heart poorly estimate the true hemodynamic state of the patient.
It is also known in the art to use noninvasive Doppler ultrasound techniques to measure the maximum blood flow velocity in the aorta or pulmonary artery and to determine cardiac output as a product of the time average mean velocity and the estimated cross-sectional area. One such usage of Doppler ultrasound techniques is described by Colley et al. in U.S. Pat. No. 4,319,580, entitled "Method for Detecting Air Emboli in the Blood in an Intracorporeal Blood Vessel", issued Mar. 16, 1982. Devices use these prior art ultrasound techniques to monitor cardiovascular hemodynamics by measuring cardiac output and stroke volume, but do not use these measurements to control cardiac functions.